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Clinical utility of C-reactive protein-based triage for presumptive pulmonary tuberculosis in South African adults

Calderwood, Claire J; Reeve, Byron WP; Mann, Tiffeney; Palmer, Zaida; Nyawo, Georgina; Mishra, Hridesh; Abubakar, Ibrahim; ... Gupta, Rishi K; + view all (2023) Clinical utility of C-reactive protein-based triage for presumptive pulmonary tuberculosis in South African adults. Journal of Infection , 86 pp. 24-32. 10.1016/j.jinf.2022.10.041. Green open access

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Abstract

BACKGROUND: Identification of an accurate, low-cost triage test for pulmonary TB among people presenting to healthcare facilities is an urgent global research priority. We assessed the diagnostic accuracy and clinical utility of C-reactive protein (CRP) for TB triage among symptomatic adult outpatients, irrespective of HIV status. METHODS: We prospectively enrolled adults reporting at least one (for people with HIV) or two (for people without HIV) symptoms of cough, fever, night sweats, or weight loss at two TB clinics in Cape Town, South Africa. Participants provided sputum for culture and Xpert MTB/RIF Ultra. We evaluated the diagnostic accuracy of CRP (measured using a laboratory-based assay) against a TB-culture reference standard as the area under the receiver operating characteristic curve (AUROC), and sensitivity and specificity at pre-specified thresholds. We assessed clinical utility using decision curve analysis and benchmarked against WHO recommendations. RESULTS: Of 932 included individuals, 255 (27%) had culture-confirmed pulmonary TB and 389 (42%) were living with HIV. CRP demonstrated an AUROC of 0·80 (95% confidence interval 0·77–0·83), with sensitivity 93% (89–95%) and specificity 54% (50–58%) using a primary cut-off of ≥10mg/L. Performance was similar among people with HIV to those without. In decision curve analysis, CRP-based triage offered greater clinical utility than confirmatory testing for all up to a number willing to test threshold of 20 confirmatory tests per true positive pulmonary TB case diagnosed (threshold probability 5%). If it is possible to perform more confirmatory tests than this, a ‘confirmatory test for all’ strategy performed better. CONCLUSIONS: CRP achieved the WHO-defined sensitivity, but not specificity, targets for a triage test for pulmonary TB and showed evidence of clinical utility among symptomatic outpatients, irrespective of HIV status.

Type: Article
Title: Clinical utility of C-reactive protein-based triage for presumptive pulmonary tuberculosis in South African adults
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jinf.2022.10.041
Publisher version: https://doi.org/10.1016/j.jinf.2022.10.041
Language: English
Additional information: Copyright © 2022 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Diagnosis, Screening, CRP, HIV, TB
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology
URI: https://discovery.ucl.ac.uk/id/eprint/10159707
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